SOMATIC COMORBIDITY PATTERNS IN PEOPLE WITH DEPRESSION: A POPULATION-BASED COHORT STUDY

Abstract People with depression often present with co-existing somatic conditions, which impact survival and steer patients’ clinical management. This study aimed to identify unique patterns of somatic comorbidity in people with depression and examine their associated mortality. We used population-based electronic health records from the Clinical Data Analysis and Reporting System in Hong Kong. People aged 40+ who had an incident depression diagnosis between 2001 and 2015 were included and followed up until 31 December 2018. Latent class analysis was applied, separately by decades, to individuals with depression and at least one comorbid somatic condition. Cox proportional hazard models were used to examine the risk of mortality associated with specific comorbidity patterns, adjusting for sociodemographic and clinical characteristics. We identified 38,889 eligible individuals (mean age: 62.8; 68.7% women). Latent class analysis identified an increasing number of patterns with age (two to seven). Compared with the unspecific pattern, the following patterns were associated with the highest mortality risk in different age groups: cardiometabolic and cerebrovascular diseases in individuals aged 40-49 (hazard ratio [HR] 2.5 [95% CI 1.7-3.7]), cardiometabolic diseases and anemia in those aged 50-59 (HR 3.4 [2.6-4.5]) and 70-79 (2.7 [2.3-3.3]), cardiometabolic, cerebrovascular diseases, and anemia in those aged 60-69 (HR 2.5 [2.0-3.2]), and cardiorespiratory disease in those aged 80+ (HR 2.0 [1.8-2.3]). Specific somatic comorbidity patterns were independently and substantially associated with the risk of mortality. This highlights the importance of taking combinations of somatic conditions into account when tailoring the clinical and care approach to people with depression.


SOCIAL DETERMINANTS OF SMOKING CESSATION IN MIDDLE-AGED AND OLDER ADULTS WITH SERIOUS MENTAL ILLNESSES
Heather Leutwyler 1 , Erin Hubbard 2 , Theodore Bussell 3 , Negin Zahedikia 4 , Dennys Balestra 1 , Margaret Wallhagen 1 , and Chizimuzo Okoli 5 , 1. University of California,San Francisco,San Francisco,California,United States,2. UCSF,San Francisco,California,United States,3. University of San Francisco School of Nursing,San Francisco,California,United States,4. University of California San Francisco,San Francisco,California,United States,5.University of Kentucky, Lexington, Kentucky, United States People living with serious mental illnesses (SMI) continue to face a disproportionate burden of tobacco-related prevalence, morbidity, and mortality as compared to those without SMI.The risk of mortality related to cigarette smoking among those with SMI is six-times that for persons without SMI.Tobacco use undermines social determinants of health (SDoH) in general and the social determinants of mental health more specifically.Not only does tobacco use exacerbate mental health symptoms, it further impedes mental health recovery by reducing expendable income, sustaining poverty, hindering food security, and limiting job opportunities.Conversely, stopping tobacco use is associated with improved mental health and, possibly, substance use recovery outcomes.The purpose of this paper is to analyze the social determinants of tobacco smoking cessation as described by adults with SMI.We conducted semi-structured qualitative interviews with 17 middle aged and older adults (mean=52, sd=6.9) with SMI upon completion of a 12-week smoking cessation program.Grounded Theory methodology guided data collection and analysis.Participants described what contributed to their success with smoking cessation or reduction and pointed out how SDoH played a role in the process.Five broad categories of SDoH described were: 1. Support and sense of belonging; 2. Structure and meaningful activities; 3. Employment; 4. Role models; and 5. Access to green space.Our findings illustrate the importance of SDoH in health interventions and are a reminder to consider these SDoH as interventions are tailored to meet the unique needs of people living with SMI.

SOMATIC COMORBIDITY PATTERNS IN PEOPLE WITH DEPRESSION: A POPULATION-BASED COHORT STUDY
Hao Luo 1 , Davide Vetrano 2 , Federico Triolo 3 , Alberto Zucchelli 4 , Yingyang Zhang 1 , Pengcheng Wang 5 , Kenneth Man 6 , and Francisco Lai 1 , 1.The University of Hong Kong,Hong Kong,Hong Kong,2. Karolinska Institutet,Solna,Stockholms Lan,Sweden,3. Aging Research Center,Solna,Stockholms Lan,Sweden,4. Università degli Studi di Brescia,Brescia,Lombardia,Italy,5. HKU,Hong Kong,Hong Kong,6. University College London,London,England,United Kingdom People with depression often present with co-existing somatic conditions, which impact survival and steer patients' clinical management.This study aimed to identify unique patterns of somatic comorbidity in people with depression and examine their associated mortality.We used population-based electronic health records from the Clinical Data Analysis and Reporting System in Hong Kong.People aged 40+ who had an incident depression diagnosis between 2001 and 2015 were included and followed up until 31 December 2018.Latent class analysis was applied, separately by decades, to individuals with depression and at least one comorbid somatic condition.Cox proportional hazard models were used to examine the risk of mortality associated with specific comorbidity patterns, adjusting for sociodemographic and clinical characteristics.We identified 38,889 eligible individuals (mean age: 62.8; 68.7% women).Latent class analysis identified an increasing number of patterns with age (two to seven).Compared with the unspecific pattern, the following patterns were associated with the highest mortality risk in different age groups: cardiometabolic and cerebrovascular diseases in individuals aged 40-49 (hazard ratio [HR] 2.5 [95% CI 1.7-3.7]),cardiometabolic diseases and anemia in those aged 50-59 ) and 70-79 (2.7 [2.3-3.3]),cardiometabolic, cerebrovascular diseases, and anemia in those aged 60-69 (HR 2.5 [2.0-3.2]), and cardiorespiratory disease in those aged 80+ (HR 2.0 [1.8-2.3]).Specific somatic comorbidity patterns were independently and substantially associated with the risk of mortality.This highlights the importance of taking combinations of somatic conditions into account when tailoring the clinical and care approach to people with depression.

CASUAL EFFECTS OF EARLY-LIFE ADVERSITY AND MID/LATE-LIFE BEHAVIORAL INTERVENTION ON THE PACE OF BIOLOGICAL AGING Chair: Daniel Belsky Discussant: Luigi Ferrucci
Epigenetic clocks have taken gerontology by storm.With the advent of 2nd and 3rd generation epigenetic clocks, including GrimAge and DunedinPACE, the field now has genomic biomarkers of aging that exhibit strong and consistent associations with aging-related morbidity and mortality.But the causes of variation in these powerful indices of aging-related biological changes remain poorly understood.In this symposium, we present four studies at the vanguard of research to elucidate causal drivers of 2nd and 3rd generation epigenetic clocks drawn from four disciplines.From life-course epidemiology, we present a natural-experiment study of the long-term impact of in-utero famine exposure.From economics, we present a quasi-natural experiment study of long-term impacts of early-life exposure to the Great Depression.From psychology, we present results from a randomized controlled trial (RCT) of cognitive behavioral therapy (CBT) for insomnia in older adults.And from geroscience, we present results from an RCT of long-term calorie restriction in healthy, non-obese adults (CALERIE).These studies report novel and important findings that suggest early-life adversity acts to accelerate the pace of biological aging -and-that it may be possible to slow the pace of biological aging in mid-and later-life through behavioral intervention.They also illustrate study designs and methods that can help move the field forward as costs for measurement of epigenetic clocks fall, enabling their introduction into many more cohort and intervention studies.

EFFECT OF LONG-TERM CALORIC RESTRICTION ON THE PACE OF BIOLOGICAL AGING IN HEALTHY ADULTS FROM THE CALERIE TRIAL Daniel Belsky, Columbia University, New York City, New York, United States
The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan.Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients, can change molecular processes associated with aging, including DNA methylation (DNAm), and increases healthy lifespan in multiple species.Here we report results of a post-hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n=220 non-obese adults were randomized to 25% CR or ad libitum control diet for 2 years.We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm clock, but did not lead to significant changes in PhenoAgeor GrimAge-clock-measured biological age.Treatment effects were small; changes in DunedinPACE suggest a ~3% slowing of the pace of aging.Nevertheless, this small effect may be substantive; in an independent study of older adults, 3% slower DunedinPACE is associated with a 15% lower risk of death.The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies and contrasting with reports that biological aging may not be modifiable.Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality.

COGNITIVE BEHAVIORAL TREATMENT OF INSOMNIA SLOWS THE PACE OF BIOLOGICAL AGING: RESULTS FROM AN RCT IN OLDER ADULTS Judith Carroll, University of California, Los Angeles, Los Angeles, California, United States
Insomnia in late life has been linked to accelerated biological aging, presenting a behaviorally modifiable target to slow the pace of aging.We previously demonstrated that treatment of insomnia in older adults using cognitive behavioral therapy for insomnia (CBT-I) reduced the expression of the cellular senescence marker, p16INK4a, in peripheral blood mononuclear cells (PBMC).Next, we tested whether this treatment for insomnia would alter the biological pace of aging, estimated from the DNA methylation derived DunedinPACE, as compared to a sleep education therapy (SET), an active comparator condition.Participants 60+ years old with insomnia were enrolled in a randomized controlled trial and assigned to CBT-I (n=49) or SET (n=45).Epigenetic data were obtained from DNA extracted from blood collected prior to initiation of treatment (baseline) and again 18-24 months later.A mixed linear models adjusting for age, sex, BMI, and education revealed a significant treatment by time interaction (p=0.003).Receipt of CBT-I was associated